The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Expression

Ubiquitous expression in lymph node (RPKM 63.6), appendix (RPKM 60.2) and 25 other tissues See more

The binding between HIV-1 Tat and Grb2 is mediated by the proline-rich sequence (residues 1-18) of Tat and the SH3 domain (residues 160-212) of Grb2, which impairs activation of the Raf/MAPK pathway and increases the PKA/Raf inhibitory pathway

Acute myeloid leukemia, organism-specific biosystemAcute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation...

Acute myeloid leukemia, conserved biosystemAcute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation...

Alcoholism, organism-specific biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...

Alcoholism, conserved biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...

Alpha 6 Beta 4 signaling pathway, organism-specific biosystemThe integrin alpha6beta4 was discovered in the late 1980s by two different groups and was called either alphaEbeta4 or Ic-Ic binding protein (Ic-IcBP) (1,2). The alpha6beta4 integrin is a component o...

Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...

B cell receptor signaling pathway, organism-specific biosystemB cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor...

B cell receptor signaling pathway, conserved biosystemB cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor...

BDNF-TrkB Signaling, organism-specific biosystemBrain-derived neurotrophic factor (BDNF) is an important neurotrophin for the regulation of synaptic activity. BDNF-TrkB signaling, TrkB being the receptor of BDNF, is involved in transcription, tran...

Breast cancer, organism-specific biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...

Breast cancer, conserved biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...

Cell surface interactions at the vascular wall, organism-specific biosystemLeukocyte extravasation is a rigorously controlled process that guides white cell movement from the vascular lumen to sites of tissue inflammation. The powerful adhesive interactions that are require...

Cell-Cell communication, organism-specific biosystemCell-to-Cell communication is crucial for multicellular organisms because it allows organisms to coordinate the activity of their cells. Some cell-to-cell communication requires direct cell-cell cont...

Chemokine signaling pathway, organism-specific biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...

Chemokine signaling pathway, conserved biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...

Choline metabolism in cancer, organism-specific biosystemAbnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, oncogenic signalling via pathways such as the RAS...

Choline metabolism in cancer, conserved biosystemAbnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, oncogenic signalling via pathways such as the RAS...

Clathrin-mediated endocytosis, organism-specific biosystemClathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1...

Constitutive Signaling by Aberrant PI3K in Cancer, organism-specific biosystemSignaling by PI3K/AKT is frequently constitutively activated in cancer via gain-of-function mutations in one of the two PI3K subunits - PI3KCA (encoding the catalytic subunit p110alpha) or PIK3R1 (en...

Constitutive Signaling by EGFRvIII, organism-specific biosystemIn glioblastoma, the most prevalent EGFR mutation, present in ~25% of tumors, is the deletion of the ligand binding domain of EGFR, accompanied with amplification of the mutated allele, which results...

Costimulation by the CD28 family, organism-specific biosystemOptimal activation of T-lymphocytes requires at least two signals. A primary one is delivered by the T-cell receptor (TCR) complex after antigen recognition and additional costimulatory signals are d...

Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...

DNA Damage Response (only ATM dependent), organism-specific biosystemThis is the second pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and TP53) which are connected with the first DNA damage response pathway. In...

Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...

Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...

Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...

EGF/EGFR Signaling Pathway, organism-specific biosystemEpidermal growth factor receptor (EGFR) also known as ErbB1/HER1 is a member of the ErbB family of receptor tyrosine kinases which also includes ErbB2 (Neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). Sev...

EGFR downregulation, organism-specific biosystemRegulation of receptor tyrosine kinase (RTK) activity is implicated in the control of almost all cellular functions. One of the best understood RTKs is epidermal growth factor receptor (EGFR). Growth...

EGFR tyrosine kinase inhibitor resistance, organism-specific biosystemEGFR is a tyrosine kinase that participates in the regulation of cellular homeostasis. EGFR also serves as a stimulus for cancer growth. EGFR gene mutations and protein overexpression, both of which ...

EGFR tyrosine kinase inhibitor resistance, conserved biosystemEGFR is a tyrosine kinase that participates in the regulation of cellular homeostasis. EGFR also serves as a stimulus for cancer growth. EGFR gene mutations and protein overexpression, both of which ...

EPO Receptor Signaling, organism-specific biosystemThe erythropoietin receptor is a 66 kDa peptide and is a member of the cytokine receptor family. The receptor is tyrosine phosphorylated upon binding by erythropoietin and associates with and activat...

Endometrial cancer, organism-specific biosystemEndometrial cancer (EC) is the most common gynaecological malignancy and the fourth most common malignancy in women in the developed world after breast, colorectal and lung cancer. Two types of endom...

Endometrial cancer, conserved biosystemEndometrial cancer (EC) is the most common gynaecological malignancy and the fourth most common malignancy in women in the developed world after breast, colorectal and lung cancer. Two types of endom...

ErbB Signaling Pathway, organism-specific biosystemThe ErbB protein family or epidermal growth factor receptor (EGFR) family is a family of four structurally related receptor tyrosine kinases. Insufficient ErbB signaling in humans is associated with ...

FCERI mediated MAPK activation, organism-specific biosystemFormation of the LAT signaling complex leads to activation of MAPK and production of cytokines. The sequence of events that leads from LAT to cytokine production has not been as clearly defined as th...

FGFR1 mutant receptor activation, organism-specific biosystemThe FGFR1 gene has been shown to be subject to activating mutations, chromosomal rearrangements and gene amplification leading to a variety of proliferative and developmental disorders depending on w...

Fc epsilon receptor (FCERI) signaling, organism-specific biosystemMast cells (MC) are distributed in tissues throughout the human body and have long been recognized as key cells of type I hypersensitivity reactions. They also play important roles in inflammatory an...

Fcgamma receptor (FCGR) dependent phagocytosis, organism-specific biosystemPhagocytosis is one of the important innate immune responses that function to eliminate invading infectious agents. Monocytes, macrophages, and neutrophils are the professional phagocytic cells. Phag...

G beta:gamma signalling through PI3Kgamma, organism-specific biosystemPI3K gamma (PI3KG) is a heterodimer consisting of a p110 catalytic subunit associated with a regulatory p101 or p84 subunit. PI3KG is most highly expressed in neutrophils, where the p101 form predomi...

G-protein beta:gamma signalling, organism-specific biosystemThe classical role of the G-protein beta/gamma dimer was believed to be the inactivation of the alpha subunit, Gbeta/gamma was viewed as a negative regulator of Galpha signalling. It is now known tha...

GAB1 signalosome, organism-specific biosystemGAB1 is recruited to the activated EGFR indirectly, through GRB2. GAB1 acts as an adaptor protein that enables formation of an active PIK3, through recruitment of PIK3 regulatory subunit PIK3R1 (also...

GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...

Gap junction, organism-specific biosystemGap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels'...

Gap junction, conserved biosystemGap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels'...

Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystemGastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic fac...

Glioma, organism-specific biosystemGliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (a...

Glioma, conserved biosystemGliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (a...

GnRH signaling pathway, organism-specific biosystemGonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnR...

GnRH signaling pathway, conserved biosystemGonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnR...

Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...

Hepatitis C and Hepatocellular Carcinoma, organism-specific biosystemPathway model based on hub miRNAs and their putative targets from network analysis. - From a set of differentially expressed genes in both chronic HCV (hepatitis C virus) and HCC (hepatocellular carc...

IL-2 Signaling Pathway, organism-specific biosystemIL-2 is a multifunctional cytokine with pleiotropic effects on several cells of the immune system. IL-2 was originally discovered as a T cell growth factor, but it was also found to have actions rela...

IL-3 Signaling Pathway, organism-specific biosystemInterleukin 3 (IL-3) is a potent growth factor belonging to the super family of cytokines. IL-3 is a 20- 32kDa glycoprotein involved in the process of hematopoiesis. It is involved in the proliferati...

IL-4 Signaling Pathway, organism-specific biosystemIL-4 is a glycoprotein which is composed of 129 amino acids and has a molecular weight of 20kDa. IL-4 and IL-13 are produced by CD4+ cells and exhibit significant functional overlap. Both these cytok...

IL-5 Signaling Pathway, organism-specific biosystemInterleukin 5 (IL-5) ligand belongs to the cytokine superfamily. IL-5 is a glycoprotein which belongs to the cytokine superfamily. It possesses the four helical bundle motifs that is conserved among ...

IL-6 signaling pathway, organism-specific biosystemIL-6 is a pleiotropic cytokine with important role in immune regulation, hematopoiesis, inflammation and oncogenesis. IL-6-type cytokines exert their action via the signal transducer gp130 that assoc...

IL-9 Signaling Pathway, organism-specific biosystemIL-9 is a multifunctional cytokine, belong to a family of cytokines. IL-9 was initially reported as a T cell growth factor in mice. It is now known to target multiple cell types. It plays an importan...

Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...

Insulin Signaling, organism-specific biosystemInsulin signaling influences energy metabolism as well as growth. The presence of insulin signals the fed state, and this signal is passed via the AKT branch, which leads to the uptake of glucose fro...

Insulin receptor signalling cascade, organism-specific biosystemAutophosphorylation of the insulin receptor triggers a series of signalling events, mediated by SHC or IRS, and resulting in activation of the Ras/RAF and MAP kinase cascades. A second effect of the ...

Insulin signaling pathway, organism-specific biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...

Insulin signaling pathway, conserved biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...

Integrin-mediated Cell Adhesion, organism-specific biosystemIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and ...

Interleukin-11 Signaling Pathway, organism-specific biosystemIL-11 is a multifunctional cytokine that belongs to the gp130 family. It was first isolated from a primate bone marrow derived cell line, PU-34 for its ability to stimulate the proliferation of a pla...

Interleukin-2 signaling, organism-specific biosystemInterleukin-2 (IL-2) is a cytokine that is produced by T cells in response to antigen stimulation. Originally, IL-2 was discovered because of its potent growth factor activity on activated T cells in...

Interleukin-3, 5 and GM-CSF signaling, organism-specific biosystemThe Interleukin-3 (IL-3), IL-5 and Granulocyte-macrophage colony stimulating factor (GM-CSF) receptors form a family of heterodimeric receptors that have specific alpha chains but share a common beta...

Jak-STAT signaling pathway, organism-specific biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...

Jak-STAT signaling pathway, conserved biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...

Leptin signaling pathway, organism-specific biosystemLeptin is a peptide hormone mainly synthesised and secreted from adipocytes. It is also expressed in other tissues including placenta, stomach and skeletal muscle. Leptin mediates its effects by bind...

Listeria monocytogenes entry into host cells, organism-specific biosystemListeria monocytogenes is a short, gram-positive, nonspore-forming motile rod. Serotypes 1/2a, 1/2b and 4b make up more than 95% of isolates from humans, with serotype 4b causing most of the food-bor...

MAPK1/MAPK3 signaling, organism-specific biosystemThe extracellular signal regulated kinases (ERKs) 1 and 2, also known as MAPK3 and MAPK1, are phosphorylated by the MAP2Ks 1 and 2 in response to a wide range of extracellular stimuli to promote diff...

Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...

MicroRNAs in cancer, organism-specific biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...

MicroRNAs in cancer, conserved biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...

NCAM signaling for neurite out-growth, organism-specific biosystemThe neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the n...

NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...

Nanoparticle-mediated activation of receptor signaling, organism-specific biosystemNanoparticle-mediated activation of receptor signaling. Several NP formulations were shown to interact with cellular receptors such as the EGFR and integrins, inducing cellular phenotypes such as pro...

Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...

Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...

Non-small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...

Non-small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...

PI-3K cascade:FGFR1, organism-specific biosystemThe ability of growth factors to protect from apoptosis is primarily due to the activation of the AKT survival pathway. P-I-3-kinase dependent activation of PDK leads to the activation of AKT which i...

PI-3K cascade:FGFR2, organism-specific biosystemThe ability of growth factors to protect from apoptosis is primarily due to the activation of the AKT survival pathway. P-I-3-kinase dependent activation of PDK leads to the activation of AKT which i...

PI-3K cascade:FGFR3, organism-specific biosystemThe ability of growth factors to protect from apoptosis is primarily due to the activation of the AKT survival pathway. P-I-3-kinase dependent activation of PDK leads to the activation of AKT which i...

PI-3K cascade:FGFR4, organism-specific biosystemThe ability of growth factors to protect from apoptosis is primarily due to the activation of the AKT survival pathway. P-I-3-kinase dependent activation of PDK leads to the activation of AKT which i...

PI3K/AKT Signaling in Cancer, organism-specific biosystemClass IA PI3K is a heterodimer of a p85 regulatory subunit (encoded by PIK3R1, PIK3R2 or PIK3R3) and a p110 catalytic subunit (encoded by PIK3CA, PIK3CB or PIK3CD). In the absence of activating signa...

PI3K/AKT activation, organism-specific biosystemPI3K/AKT signalling is a major regulator of neuron survival. It blocks cell death by both impinging on the cytoplasmic cell death machinery and by regulating the expression of genes involved in cell...

PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling, organism-specific biosystemPhosphatidylinositol-5-phosphate (PI5P) may modulate PI3K/AKT signaling in several ways. PI5P is used as a substrate for production of phosphatidylinositol-4,5-bisphosphate, PI(4,5)P2 (Rameh et al. 1...

PIP3 activates AKT signaling, organism-specific biosystemSignaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimula...

Phospholipase D signaling pathway, organism-specific biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...

Phospholipase D signaling pathway, conserved biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...

Pilocytic astrocytoma, organism-specific biosystemIn this pathway shows the signaling in the development and behavior of the disease. receptor tyrosine kinase(rtk) is expressed in tumor endothelial cells of adult glioblastomas.NF1 and BRAF genes in...

Platelet Aggregation (Plug Formation), organism-specific biosystemThe tethering of platelets to the site of vascular injury is the first step in the formation of a platelet thrombus. Firm adhesion of these tethered platelets, as well as the additional recruitment o...

Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...

Prolactin signaling pathway, organism-specific biosystemProlactin (PRL) is a polypeptide hormone known to be involved in a wide range of biological functions including osmoregulation, lactation, reproduction, growth and development, endocrinology and meta...

Prolactin signaling pathway, conserved biosystemProlactin (PRL) is a polypeptide hormone known to be involved in a wide range of biological functions including osmoregulation, lactation, reproduction, growth and development, endocrinology and meta...

Prostate cancer, organism-specific biosystemProstate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of...

Prostate cancer, conserved biosystemProstate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of...

Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...

Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...

RHO GTPases Activate WASPs and WAVEs, organism-specific biosystemWASP and WAVE proteins belong to the Wiskott-Aldrich Syndrome protein family, with recessive mutations in the founding member WASP being responsible for the X-linked recessive immunodeficieny known a...

Regulation of actin dynamics for phagocytic cup formation, organism-specific biosystemThe actin cytoskeleton is fundamental for phagocytosis and members of the Rho family GTPases RAC and CDC42 are involved in actin cytoskeletal regulation leading to pseudopod extension. Active RAC and...

Renal cell carcinoma, organism-specific biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...

Renal cell carcinoma, conserved biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...

Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystemThe lipid raft resident adaptor molecules LAT1 and Non-T cell activation linker (NTAL), also known as linker for activation of B cells (LAB)/LAT2 are known participants in the regulation of mast cell...

SHC-mediated cascade:FGFR1, organism-specific biosystemThe exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction...

SHC-mediated cascade:FGFR2, organism-specific biosystemThe exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction...

SHC-mediated cascade:FGFR3, organism-specific biosystemThe exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction...

SHC-mediated cascade:FGFR4, organism-specific biosystemThe exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction...

Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...

Signal regulatory protein (SIRP) family interactions, organism-specific biosystemSignal regulatory protein (SIRP)alpha, also known as SHPS-1 or SIRPA or CD172a, is a transmembrane protein expressed mostly on myeloid cells. CD47, a widely expressed transmembrane protein, is a liga...

Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...

Signaling by EGFR in Cancer, organism-specific biosystemThe pathway "Signaling by EGFR in Cancer" shows signaling by constitutively active EGFR cancer variants in the context of "Signaling by EGFR", allowing users to compare cancer events with the wild-ty...

Signaling by EGFRvIII in Cancer, organism-specific biosystemEGFRvIII (EGFR V30_R297delinsG) is the most prevalent EGFR variant in glioblastoma, but it is also found in other cancer types. In-frame deletion of the ligand binding domain in EGFRvIII is frequentl...

Signaling by ERBB2, organism-specific biosystemERBB2, also known as HER2 or NEU, is a receptor tyrosine kinase (RTK) belonging to the EGFR family. ERBB2 possesses an extracellular domain that does not bind any known ligand, contrary to other EGFR...

Signaling by ERBB4, organism-specific biosystemERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular lig...

Signaling by FGFR, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...

Signaling by FGFR in disease, organism-specific biosystemA number of skeletal and developmental diseases have been shown to arise as a result of mutations in the FGFR1, 2 and 3 genes. These include dwarfism syndromes (achondroplasia, hypochondroplasia and...

Signaling by FGFR1, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...

Signaling by FGFR1 in disease, organism-specific biosystemThe FGFR1 gene has been shown to be subject to activating mutations, chromosomal rearrangements and gene amplification leading to a variety of proliferative and developmental disorders depending on w...

Signaling by FGFR2, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...

Signaling by FGFR2 in disease, organism-specific biosystemThe FGFR2 gene has been shown to be subject to activating mutations and gene amplification leading to a variety of proliferative and developmental disorders depending on whether these events occur in...

Signaling by FGFR3, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...

Signaling by FGFR3 fusions in cancer, organism-specific biosystemIn recent years, recurrent fusions of FGFR3 have been identified in a number of cancers, including glioblastoma and cancers of the lung and bladder, among others (Singh et al, 2012; Parker et al, 201...

Signaling by FGFR3 in disease, organism-specific biosystemThe FGFR3 gene has been shown to be subject to activating mutations and gene amplification leading to a variety of proliferative and developmental disorders depending on whether these events occur in...

Signaling by FGFR3 point mutants in cancer, organism-specific biosystemThe FGFR3 gene has been shown to be subject to activating mutations and gene amplification leading to a variety of proliferative and developmental disorders depending on whether these events occur in...

Signaling by FGFR4, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...

Signaling by FGFR4 in disease, organism-specific biosystemFGFR4 is perhaps the least well studied of the FGF receptors, and unlike the case for the other FGFR genes, mutations in FGFR4 are not known to be associated with any developmental disorders. Recent...

Signaling by Insulin receptor, organism-specific biosystemInsulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (e.g. IRS and Shc) by the insulin receptor...

Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...

Signaling by Ligand-Responsive EGFR Variants in Cancer, organism-specific biosystemLigand-responsive EGFR cancer variants harbor mutations in the kinase domain or point mutations in the extracellular domain. These altered EGFR proteins are able to signal in the absence of ligands, ...

Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...

Signaling by Rho GTPases, organism-specific biosystemThe Rho family of small guanine nucleotide binding proteins is one of five generally recognized branches of the Ras superfamily. Like most Ras superfamily members, typical Rho proteins function as bi...

Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...

Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...

Signaling by cytosolic FGFR1 fusion mutants, organism-specific biosystem8p11 myeloproliferative syndrome (EMS) is an aggressive disorder that is associated with a translocation event at the FGFR1 gene on chromosome 8p11. Typical symptoms upon diagnosis include eosinophi...

Signaling pathways regulating pluripotency of stem cells, organism-specific biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...

Signaling pathways regulating pluripotency of stem cells, conserved biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...

Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...

Signalling to ERKs, organism-specific biosystemNeurotrophins utilize multiple pathways to activate ERKs (ERK1 and ERK2), a subgroup of the large MAP kinase (MAPK) family, from the plasma membrane. The major signalling pathways to ERKs are via RAS...

Signalling to RAS, organism-specific biosystemSignalling through Shc adaptor proteins appears to be identical for both NGF and EGF. It leads to a fast, but transient, MAPK/ERK activation, which is insufficient to explain the prolonged activation...

Spry regulation of FGF signaling, organism-specific biosystemSprouty was initially characterized as a negative regulator of FGFR signaling in Drosophila. Human cells contain four genes encoding Sprouty proteins, of which Spry2 is the best studied and most wid...

T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...

T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...

Tie2 Signaling, organism-specific biosystemThe Tie2/Tek receptor tyrosine kinase plays a pivotal role in vascular and hematopoietic development and is expressed exclusively on endothelial lineage. Tie2 interacts with a group of ligands belong...

VEGFA-VEGFR2 Pathway, organism-specific biosystemAngiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic...

Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...

Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...

Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...

p38 MAPK Signaling Pathway, organism-specific biosystemp38 MAPKs are members of the MAPK family that are activated by a variety of environmental stresses and inflammatory cytokines. Stress signals are delivered to this cascade by members of small GTPases...

These reference sequences are curated independently of the genome
annotation cycle, so their versions may not match the RefSeq versions in the current
genome build. Identify version mismatches by comparing the version of the RefSeq in
this section to the one reported in Genomic regions,
transcripts, and products above.

Transcript Variant: This variant (2) lacks an in-frame exon in the 3' coding region, as compared to variant 1. It encodes the shorter isoform (2) that lacks an internal segment, as compared to isoform 1.

The following sections contain reference sequences that belong to a
specific genome build. Explain

This section includes genomic Reference
Sequences (RefSeqs) from all assemblies on which this gene is annotated, such as
RefSeqs for chromosomes and scaffolds (contigs) from both reference and alternate
assemblies. Model RNAs and proteins are also reported here.